is a member of the cytochrome P450 superfamily of enzymes localized in the endoplasmic reticulum. Proteins in this family are monooxygenases that catalyze synthesis of cholesterol, steroids and other lipids and are involved in drug metabolism. CYP17A1 has both 17α-hydroxylase activity () and 17,20-lyase activity (). The 17α-hydroxylase activity of CYP17A1 is required for the generation of glucocorticoids such as cortisol, but both the hydroxylase and 17,20-lyase activities of CYP17A1 are required for the production of androgenic and oestrogenic sex steroids by converting 17α-hydroxypregnenolone to dehydroepiandrosterone (DHEA). Mutations in this gene are associated with isolated steroid-17α-hydroxylase deficiency, 17α-hydroxylase/17,20-lyase deficiency, pseudohermaphroditism, and adrenal hyperplasia. Furthermore, the 17,20-lyase activity is dependent on cytochrome P450 oxidoreductase (POR) cytochrome b5 (CYB5) and phosphorylation. Cytochrome b5 acts as a facilitator for 17,20 lyase activity of CYP17A1 and can donate a second electron to some P450s. In humans the production of testosterone via pregnenolone to17-OHPreg and DHEA by the CYP17A1 requires POR. Human CYP17A1 protein is phosphorylated on serine and threonine residues by a cAMP-dependent protein kinase. Phosphorylation of the protein increases 17,20-lyase activity, while dephosphorylation virtually eliminates this activity. Clinical significance Mutations in this gene are associated with rare forms of congenital adrenal hyperplasia, specifically 17α-hydroxylase deficiency/17,20-lyase deficiency and isolated 17,20-lyase deficiency. In humans, the CYP17A1 gene is largely associated with endocrine effects and steroid hormone metabolism. Furthermore, mutations in the CYP17A1 gene are associated with rare forms of congenital adrenal hyperplasia, in particular 17α-hydroxylase deficiency/17,20-lyase deficiency and isolated 17,20-lyase deficiency. Overall, CYP17A1 is an important target for inhibition in the treatment of prostate cancer because it produces androgen that is required for tumor cell growth. The decreased enzyme activity of CYP17A1 is related to infertility due to hypogonadotropic hypogonadism. In females, folliculogenesis is arrested, while in males, testicular atrophy with interstitial cell proliferation and arrested spermatogenesis. Although generally anovulatory, there are some case reports of women with 17α-hydroxylase deficiency who underwent spontaneous menarche with cyclic menses. Clinical marker A multi-locus genetic risk score study based on a combination of 27 loci, including the CYP17A1 gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE